Trypanosoma cruzi,the causative agent of American trypanosomiasis or Chagas' disease, is of both medical and veterinary importance as is evidenced by chronic phase myocarditis in humans and dogs. Further, T. cruzihas been reported from over 20 species of wildlife reservoir hosts in the USA, with raccoons (Procyon lotor) and opossums (Didelphis virginiana) being the most common. Whereas previous studies on T. cruziin raccoons have included only culture and direct examination of blood, the indirect immunofluorescent antibody test (IFAT) was used in the current study to detect anti-T. cruziantibodies in the serum of raccoons. Of 221 raccoons trapped at 13 sites representing the five physiographic regions of South Carolina plus five sites in the Piedmont region of Georgia (from April 1997 to February 2000), 104 (47%) were seropositive. A higher seroprevalence in raccoons was observed in the coastal regions, with seroprevalence in the Lower Coastal Plain South (61%) being significantly higher than that in the Foothills (37%), Piedmont (42%), and Upper Coastal Plain (40%) regions. However, at a seroprevalence of 52%, the Lower Coastal Plain North was not significantly different from any other region. Although more female raccoons were infected than males, no statistical difference in prevalence was observed between sexes. The high seroprevalence of T. cruziin raccoons, together with a few reports of wildlife isolates being infective for other wildlife species and domestic/laboratory animals, suggests that risk of T. cruziinfection may be higher than previously suspected.